This is a competing renewal application for a K24 Mid-Career Award in Patient-Oriented Research for Richard E. Chaisson, MD, of the Johns Hopkins University School of Medicine. The applicant's original award proposed to provide support for patient oriented research on tuberculosis control in developing countries, mentoring of junior faculty and fellows in clinical research, and leadership of the Johns Hopkins Center for TB Research, which was founded at the time of the original award. All three aims have been executed with outstanding results. Dr. Chaisson's proposed community-randomized trial of alternative TB control strategies has been undertaken with support from a ICIDR program project grant and results will be available within a year. He has mentored a half-dozen junior faculty members and number of fellows, with notable success in terms of publications, funding and promotion. Finally, he has led the growth of the Center for TB Research from a $3 million enterprise to a world renowned center of excellence with more than $60 million in research funding. This recompetition application proposed to continue the leadership and management of the Center for TB Research, provide ongoing mentoring to five junior faculty and to fellows and graduate students, and to conduct innovative research on TB control strategies in developing countries by conducting a cluster-randomized, phase implementation study of INH preventive therapy for HIV-infected patients in Rio de Janeiro, Brazil. Support for these activities will enable Dr. Chaisson to further strengthen and expand the scope of the Center for TB Research, assist young investigators with academic advancement and success, and contribute to global tuberculosis control by developing new paradigms for reducing the burden of HIV-related TB.